title: RUNX1 meets MLL: epigenetic regulation of hematopoiesis by two leukemia genes.
abstract: A broad range of human leukemias carries RUNX1 and MLL genetic alterations. Despite such widespread involvements, the relationship between RUNX1 and MLL has never been appreciated. Recently, we showed that RUNX1 physically and functionally interacts with MLL, thereby regulating the epigenetic status of critical cis-regulatory elements for hematopoietic genes. This newly unveiled interaction between the two most prevalent leukemia genes has solved a long-standing conundrum: leukemia-associated RUNX1 N-terminal point mutants that exhibit no obvious functional abnormalities in classical assays for the assessment of transcriptional activities. These mutants turned out to be defective in MLL interaction and subsequent epigenetic modifications that can be examined by the histone-modification status of cis-regulatory elements in the target genes. RUNX1/MLL binding confirms the importance of RUNX1 function as an epigenetic regulator. Recent studies employing next-generation sequencing on human hematological malignancies identified a plethora of mutations in epigenetic regulator genes. These new findings would enhance our understanding on the mechanistic basis for leukemia development and may provide a novel direction for therapeutic applications. This review summarizes the current knowledge about the epigenetic regulation of normal and malignant hematopoiesis by RUNX1 and MLL.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: C P
authors.initials: CP
authors.lastname: Koh
authors.forename: C Q
authors.initials: CQ
authors.lastname: Wang
authors.forename: C E L
authors.initials: CE
authors.lastname: Ng
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Araki
authors.forename: V
authors.initials: V
authors.lastname: Tergaonkar
authors.forename: G
authors.initials: G
authors.lastname: Huang
authors.forename: M
authors.initials: M
authors.lastname: Osato
mesh_terms: D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D015973:Gene Expression Regulation, Leukemic; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D051788:Myeloid-Lymphoid Leukemia Protein